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1.
Melatonin Confers Plant Cadmium Tolerance: An Update.
Gu, Q, Wang, C, Xiao, Q, Chen, Z, Han, Y
International journal of molecular sciences. 2021;(21)
Abstract
Cadmium (Cd) is one of the most injurious heavy metals, affecting plant growth and development. Melatonin (N-acetyl-5-methoxytryptamine) was discovered in plants in 1995, and it is since known to act as a multifunctional molecule to alleviate abiotic and biotic stresses, especially Cd stress. Endogenously triggered or exogenously applied melatonin re-establishes the redox homeostasis by the improvement of the antioxidant defense system. It can also affect the Cd transportation and sequestration by regulating the transcripts of genes related to the major metal transport system, as well as the increase in glutathione (GSH) and phytochelatins (PCs). Melatonin activates several downstream signals, such as nitric oxide (NO), hydrogen peroxide (H2O2), and salicylic acid (SA), which are required for plant Cd tolerance. Similar to the physiological functions of NO, hydrogen sulfide (H2S) is also involved in the abiotic stress-related processes in plants. Moreover, exogenous melatonin induces H2S generation in plants under salinity or heat stress. However, the involvement of H2S action in melatonin-induced Cd tolerance is still largely unknown. In this review, we summarize the progresses in various physiological and molecular mechanisms regulated by melatonin in plants under Cd stress. The complex interactions between melatonin and H2S in acquisition of Cd stress tolerance are also discussed.
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2.
Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities.
Talib, WH, Alsayed, AR, Abuawad, A, Daoud, S, Mahmod, AI
Molecules (Basel, Switzerland). 2021;(9)
Abstract
Melatonin is a pleotropic molecule with numerous biological activities. Epidemiological and experimental studies have documented that melatonin could inhibit different types of cancer in vitro and in vivo. Results showed the involvement of melatonin in different anticancer mechanisms including apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy, and augmentation of the therapeutic effects of conventional anticancer therapies. Clinical trials revealed that melatonin is an effective adjuvant drug to all conventional therapies. This review summarized melatonin biosynthesis, availability from natural sources, metabolism, bioavailability, anticancer mechanisms of melatonin, its use in clinical trials, and pharmaceutical formulation. Studies discussed in this review will provide a solid foundation for researchers and physicians to design and develop new therapies to treat and prevent cancer using melatonin.
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3.
Does Evidence Exist to Blunt Inflammatory Response by Nutraceutical Supplementation during COVID-19 Pandemic? An Overview of Systematic Reviews of Vitamin D, Vitamin C, Melatonin, and Zinc.
Corrao, S, Mallaci Bocchio, R, Lo Monaco, M, Natoli, G, Cavezzi, A, Troiani, E, Argano, C
Nutrients. 2021;(4)
Abstract
More than one year has passed since the first cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-CoV-2 coronavirus were reported in Wuhan (China), rapidly evolving into a global pandemic. This infectious disease has become a major public health challenge in the world. Unfortunately, to date, no specific antivirals have been proven to be effective against COVID-19, and although a few vaccines are available, the mortality rate is not decreasing but is still increasing. One therapeutic strategy has been focused on infection prevention and control measures. In this regard, the use of nutraceutical supports may play a role against some aspect of the infection, particularly the inflammatory state and the immune system function of patients, thus representing a strategy to control the worst outcomes of this pandemic. For this reason, we performed an overview including meta-analyses and systematic reviews to assess the association among melatonin, vitamin C, vitamin D, zinc supplementation and inflammatory markers using three databases, namely, MEDLINE, PubMed Central and the Cochrane Library of Systematic Reviews. According to the evidence available, an intake of 50,000 IU/month of vitamin D showed efficacy in CRP. An amount of 1 to 2 g per day of vitamin C demonstrated efficacy both in CRP and endothelial function, and a dosage of melatonin ranging from 5 to 25 mg /day showed good evidence of efficacy in CRP, TNF and IL6. A dose of 50 mg/day of elemental zinc supplementation showed positive results in CRP. Based on the data reported in this review, the public health system could consider whether it is possible to supplement the current limited preventive measures through targeted nutraceutical large-scale administration.
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4.
Melatonin interferes with COVID-19 at several distinct ROS-related steps.
Camp, OG, Bai, D, Gonullu, DC, Nayak, N, Abu-Soud, HM
Journal of inorganic biochemistry. 2021;:111546
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Abstract
Recent studies have shown a correlation between COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the distinct, exaggerated immune response titled "cytokine storm". This immune response leads to excessive production and accumulation of reactive oxygen species (ROS) that cause clinical signs characteristic of COVID-19 such as decreased oxygen saturation, alteration of hemoglobin properties, decreased nitric oxide (NO) bioavailability, vasoconstriction, elevated cytokines, cardiac and/or renal injury, enhanced D-dimer, leukocytosis, and an increased neutrophil to lymphocyte ratio. Particularly, neutrophil myeloperoxidase (MPO) is thought to be especially abundant and, as a result, contributes substantially to oxidative stress and the pathophysiology of COVID-19. Conversely, melatonin, a potent MPO inhibitor, has been noted for its anti-inflammatory, anti-oxidative, anti-apoptotic, and neuroprotective actions. Melatonin has been proposed as a safe therapeutic agent for COVID-19 recently, having been given with a US Food and Drug Administration emergency authorized cocktail, REGEN-COV2, for management of COVID-19 progression. This review distinctly highlights both how the destructive interactions of HOCl with tetrapyrrole rings may contribute to oxygen deficiency and hypoxia, vitamin B12 deficiency, NO deficiency, increased oxidative stress, and sleep disturbance, as well as how melatonin acts to prevent these events, thereby improving COVID-19 prognosis.
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5.
Role of Melatonin in Angiotensin and Aging.
Sehirli, AO, Sayıner, S, Chukwunyere, U, Serakinci, N
Molecules (Basel, Switzerland). 2021;(15)
Abstract
The cellular utilization of oxygen leads to the generation of free radicals in organisms. The accumulation of these free radicals contributes significantly to aging and several age-related diseases. Angiotensin II can contribute to DNA damage through oxidative stress by activating the NAD(P)H oxidase pathway, which in turn results in the production of reactive oxygen species. This radical oxygen-containing molecule has been linked to aging and several age-related disorders, including renal damage. Considering the role of angiotensin in aging, melatonin might relieve angiotensin-II-induced stress by enhancing the mitochondrial calcium uptake 1 pathway, which is crucial in preventing the mitochondrial calcium overload that may trigger increased production of reactive oxygen species and oxidative stress. This review highlights the role and importance of melatonin together with angiotensin in aging and age-related diseases.
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Effects of Melatonin Supplementation on Insulin Levels and Insulin Resistance: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Li, Y, Xu, Z
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2021;(9):616-624
Abstract
Insulin resistance (IR) is a pivotal process in various metabolic diseases. The well-known treatment is lifestyle modification and medication therapy, which may result in poor compliance and side effects. Melatonin has been suggested to have a role in glucose metabolism, yet the results across studies have been inconsistent. Therefore, we performed a systematic review to evaluate the effects of melatonin supplementation on insulin levels and IR. We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov, and identified randomized controlled trials (RCTs) published prior to August 2020. Articles were reviewed, selected and extracted by two reviewers independently. In total, 8 RCTs of 376 participants were included. Data were pooled using a random-effects model, with mean differences (MDs) and 95% confidence intervals (CIs). Our results showed that melatonin administration significantly reduced insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR), and increased the quantitative insulin sensitivity check index (QUICKI). We conclude that melatonin ameliorated hyperinsulinemia, insulin resistance, and insulin sensitivity, and the results are an update of a previous meta-analysis. Although more investigations are required, we clearly provide evidence for the use of melatonin as an adjuvant treatment for metabolic disorders involving IR.
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7.
Metal ion homeostasis with emphasis on zinc and copper: Potential crucial link to explain the non-classical antioxidative properties of vitamin D and melatonin.
Martín Giménez, VM, Bergam, I, Reiter, RJ, Manucha, W
Life sciences. 2021;:119770
Abstract
Metal ion homeostasis is an essential physiological mechanism necessary for achieving an adequate balance of these ions' concentrations in the different cellular compartments. This fact is of great importance because both an excess and a deficiency of cellular metal ion levels are usually equally harmful due to the exacerbated increase in oxidative stress that may occur in both cases. Metal ion homeostasis ensures an equilibrium among multiple functions associated with the body's antioxidative defense network controlled by metallic micronutrients such as zinc and copper, some of the central regulators of redox processes. These micronutrients significantly modulate the activity of some isoforms of superoxide dismutase (SOD) and other enzymes such as metallothioneins (MTs) and ceruloplasmin (CP), which are directly or indirectly involved in the regulation of redox homeostasis. Although it is well known that both melatonin (MEL) and vitamin D have important roles as natural antioxidants, often some of these effects are related to their actions on antioxidative processes dependent on metal ions. Thus, in addition to their classical antioxidative properties usually associated with mitochondrial effects, it is known that MEL and vitamin D modulate the expression and activity of Cu/Zn-dependent SOD isoforms, MTs and CP; function as copper chelators and regulate genomic and non-genomic mechanisms related to the zinc transport. This review summarizes the main findings related to the crucial participation of zinc and copper in physiological antioxidative status and their relationship with the non-classical antioxidant effects of MEL and vitamin D, suggesting a potential synergism among these four micronutrients.
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8.
Multiple interactions between melatonin and non-coding RNAs in cancer biology.
Maleki, M, Khelghati, N, Alemi, F, Younesi, S, Asemi, Z, Abolhasan, R, Bazdar, M, Samadi-Kafil, H, Yousefi, B
Chemical biology & drug design. 2021;(3):323-340
Abstract
The melatonin hormone secreted by the pineal gland is involved in physiological functions such as growth and maturation, circadian cycles, and biological activities including antioxidants, anti-tumor, and anti-ischemia. Melatonin not only interacts with proteins but also has functional effects on regulatory RNAs such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). In this study, we overview various physiological and pathological conditions affecting melatonin through lncRNA and miRNA. The information compiled herein will serve as a solid foundation to formulate ideas for future mechanistic studies on melatonin. It will also provide a chance to more clarify the emerging functions of the non-coding transcriptome.
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9.
Melatonin: A master regulator of plant development and stress responses.
Sun, C, Liu, L, Wang, L, Li, B, Jin, C, Lin, X
Journal of integrative plant biology. 2021;(1):126-145
Abstract
Melatonin is a pleiotropic molecule with multiple functions in plants. Since the discovery of melatonin in plants, numerous studies have provided insight into the biosynthesis, catabolism, and physiological and biochemical functions of this important molecule. Here, we describe the biosynthesis of melatonin from tryptophan, as well as its various degradation pathways in plants. The identification of a putative melatonin receptor in plants has led to the hypothesis that melatonin is a hormone involved in regulating plant growth, aerial organ development, root morphology, and the floral transition. The universal antioxidant activity of melatonin and its role in preserving chlorophyll might explain its anti-senescence capacity in aging leaves. An impressive amount of research has focused on the role of melatonin in modulating postharvest fruit ripening by regulating the expression of ethylene-related genes. Recent evidence also indicated that melatonin functions in the plant's response to biotic stress, cooperating with other phytohormones and well-known molecules such as reactive oxygen species and nitric oxide. Finally, great progress has been made towards understanding how melatonin alleviates the effects of various abiotic stresses, including salt, drought, extreme temperature, and heavy metal stress. Given its diverse roles, we propose that melatonin is a master regulator in plants.
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10.
Blood-brain barrier dysfunction in hemorrhagic transformation: a therapeutic opportunity for nanoparticles and melatonin.
Figueroa, EG, González-Candia, A, Caballero-Román, A, Fornaguera, C, Escribano-Ferrer, E, García-Celma, MJ, Herrera, EA
Journal of neurophysiology. 2021;(6):2025-2033
Abstract
Stroke is the second leading cause of death worldwide, estimated that one-sixth of the world population will suffer it once in their life. The most common type of this medical condition is the ischemic stroke (IS), produced by a thrombotic or embolic occlusion of a major cerebral artery or its branches, leading to the formation of a complex infarct region caused by oxidative stress, excitotoxicity, and endothelial dysfunction. Nowadays, the immediate treatment for IS involves thrombolytic agents or mechanical thrombectomy, depending on the integrity of the blood-brain barrier (BBB). A common stroke complication is the hemorrhagic transformation (HT), which consists of bleeding into the ischemic brain area. Currently, better treatments for IS are urgently needed. As such, the neurohormone melatonin has been proposed as a good candidate due to its antioxidant, anti-inflammatory, and neuroprotective effects, particularly against lipid peroxidation and oxidative stress during brain ischemia. Here, we proposed to develop intravenous or intranasal melatonin nanoformulation to specifically target the brain in patients with stroke. Nowadays, the challenge is to find a formulation able to cross the barriers and reach the target organ in an effective dose to generate the pharmacological effect. In this review, we discuss the current literature about stroke pathophysiology, melatonin properties, and its potential use in nanoformulations as a novel therapeutic approach for ischemic stroke.